Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats

doi:10.1016/j.bone.2007.10.013

Bone

Volume 42, Issue 2, February 2008, Pages 365-371

https://doi.org/10.1016/j.bone.2007.10.013 Get rights and content

Abstract

Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix leads to an enhancement of the pullout strength 2 weeks after insertion in rat tibiae. This effect then increases over time until at least 8 weeks. The pullout force reflects the mechanical properties of the bone within the threads, which acts as a screw nut. The aim of the present study was to find descriptive and morphometric histological correlates to the increased pullout strength. Because the bisphosphonates are applied via the implant surface, we also measured bone to implant contact and how far away from the surface any effects could be seen.

Stainless steel screws underwent one of three treatments: uncoated control, controls coated with a layer of cross-linked fibrinogen, or screws further modified with bisphosphonates covalently linked and physically adsorbed to the fibrinogen layer. At 1 (n = 33) and 8 (n = 27) weeks, bone to implant contact and bone area density in the threads were measured, as well as bone area density at 250 and 500 μm from the outer edge of the threads. Additionally, removal torque for each screw treatment was measured at 2 weeks (n = 28).

At 8 weeks, the part of the bisphosphonate screw that was located in the marrow cavity had become surrounded with bone, whereas there was almost no bone surrounding the controls. The bone area density in the threads along the entire bisphosphonate screw was increased by 40% compared with uncoated controls, and at 250 μm distance it was more than doubled. At 1 week, coated screws had less implant–bone contact, but at 8 weeks there was no difference between uncoated and bisphosphonate-coated screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks compared to uncoated screws. Howship's lacunae and osteoclasts were found near the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling took place near the implant, in spite of the presence of bisphosphonates.

Introduction

Early rigid fixation of an implant to bone is important for its long-term results. Hip or knee replacements that show increased early migration relative to the bone during the first one or two years have a dramatically increased risk of loosening, which often becomes apparent first several years later [1], [2], [3].

Implant insertion in cancellous bone leads to an inflammatory response, followed by release of cytokines and growth factors which eventually stimulate differentiation of bone forming cells [4]. These cells produce primitive woven bone, which is then remodeled to lamellar bone. However, it appears that resorption and formation during this remodeling are not always coupled. Consider fracture repair: not only can a bone callus grow as a result of predominant formation, but it can also diminish as a result of predominant resorption. This can be observed in almost all fractures. Similarly, the timing of the dominance of formation or resorption around an implant may partly determine how much bone will surround it. Thus, if resorption can be reduced or delayed, formation may still be increased, leading to a net increase in the amount of bone. Indeed, the early migration of knee prostheses can be reduced if bisphosphonates are given either systemically or applied directly to the bone surface prior to insertion of the prostheses [5], [6].

We have previously applied bisphosphonates to the surface of stainless steel screws, implanted them in rat bone and found that the pullout strength gradually increased for up to 8 weeks [7], [8]. The pullout force reflects the macromechanical properties of the bone within the threads, which can be said to act as a screw nut. The mechanical results call for a histological examination to clarify their structural background. We hypothesized that the previously observed gradual increase in fixation was due to an increasing amount of bone forming around the screw. Secondarily, we wanted to describe how far away from the implant bisphosphonate-induced changes could be seen and if there was an effect on bone implant contact. Finally, we studied if the bisphosphonates influenced removal torque, as a mechanical counterpart to bone implant contact.

Section snippets

Materials and methods

The fixation of stainless steel screws was studied in 2 experiments; Morphophometric study and Removal torque study. For both of these studies, the preparation of the bisphosphonate-coated screws was executed according to the same protocol. A multilayer of fibrinogen was covalently bound to the screws followed by the binding of two types of bisphosphonates, one covalently linked, and one adsorbed. In order to estimate the coated film thickness on the screws, flat silicon surfaces were treated

Animals

Seven rats died during anesthesia. In the Morphometric study, two samples were destroyed in the polishing machine. In the Removal torque study, one screw was misimplanted and the rat was excluded at surgery. One screw was accidentally loosened before measuring. The number of remaining rats is given in Table 3A.

Qualitative results

About one third of the length of the screw was located in cortical bone, and the remaining part in the marrow cavity. At 1 week, scattered areas of primitive bone or osteoid were seen in

Discussion

Several studies have shown an improved fixation of bisphosphonate-coated implants in bone [11], [12], [13], [14], [15], [16], [17]. Also an increased bone density at some distance from the implant has been described [11], [13], [14], [15], [16]. The novelty of this study lies in the method used for applying the bisphosphonates and our finding of a sleeve of new bone around the bisphosphonate-coated screws in the marrow cavity. This was morphometrically confirmed by an increase in average bone

Acknowledgments

The authors thank Bibbi Mård for technical assistance. This investigation was supported by the local Strategic research projects Materials in Medicine (Östergötlands läns landsting, Linköpings universitet), and the Swedish Research Council (project 2031).

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View full text

Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats

Abstract

Introduction

Section snippets

Materials and methods

Animals

Qualitative results

Discussion

Acknowledgments

Biomaterials

J Orthop Res

Bone

Biomaterials

J Biol Chem

Biomaterials

The theory of early loosening of hip prostheses

Orthopedics

Roentgen stereophotogrammetric analysis of prosthetic fixation in the hip and knee joint

Clin Orthop Relat Res

Does early micromotion of femoral stem prostheses matter? 4–7-year stereoradiographic follow-up of 84 cemented prostheses

J Bone Jt Surg Br

The cell and molecular biology of fracture healing

Clin Orthop Relat Res

Clodronate prevents prosthetic migration: a randomized radiostereometric study of 50 total knee patients

Acta Orthop Scand